Refractory celiac disease

Abstract

A small subset of celiac disease (CD) patients becomes refractory to a gluten-free diet with persistent malabsorption and intestinal villous atrophy. Diagnosis of this condition defined as refractory celiac disease (RCD) is made after exclusion of other small bowel diseases with villous atrophy. RCD has been subdivided into two subgroups according to the normal or abnormal phenotype of intraepithelial lymphocytes. Whereas normal RCD is hardly distinguishable from active CD, abnormal RCD has a severe clinical presentation and a very poor prognosis. We precisely describe below the different types of RCD and propose diagnostic and therapeutic guidelines for its clinical management.

Keywords::

• aberrant intraepithelial lymphocytes
• clonal rearrangement
• refractory celiac disease
• T cell receptor
• ulcerative jejunitis

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The concept of refractory celiac disease (RCD) has recently emerged and refers to two distinct entities.

• RCDI is indistinguishable from active CD except in its autonomy toward gluten exposure.

• RCDII is defined as a low-grade intestinal lymphoma characterized by clonal expansion of abnormal intestinal intraepithelial lymphocytes.

• Small bowel endoscopy such as double-balloon enteroscopy with biopsy helps with the diagnosis.

• Specialized analysis of intestinal intraepithelial lymphocytes including immunohistochemistry, flow cytometry of isolated intestinal lymphocytes and multiplex PCR are required for diagnosis.

• Survival of patients with RCDI is slightly inferior to that of those with celiac disease.

• Five-year survival rate of patients with RCDII is around 50%. This poor prognosis is due to severe malnutrition and increased risk of overt lymphoma.

• Advances in the understanding of pathogenic mechanisms of RCD, particularly in RCDII, offer new therapeutic targets by inhibiting IL-15 effects.